The Effect of Menstrual Cycle and Contraceptives on ACL Injuries and Laxity: A Systematic Review and Meta-analysis

Simone D Herzberg, Makalapua L Motu'apuaka, William Lambert, Rongwei Fu, Jacqueline Brady, Jeanne-Marie Guise, Simone D Herzberg, Makalapua L Motu'apuaka, William Lambert, Rongwei Fu, Jacqueline Brady, Jeanne-Marie Guise

Abstract

Background: Women are at substantially greater risk for anterior cruciate ligament (ACL) injuries than are men.

Purpose: To conduct a systematic review and meta-analysis of the literature to clarify the effect of the menstrual cycle and contraceptives on the laxity of and noncontact injuries to the ACL.

Study design: Systematic review; Level of evidence, 4.

Methods: Searches were conducted using MEDLINE (1946-August 2016), the Cochrane Library Database, clinical trial registries, and related reference lists. Search terms included athletic injuries, knee injuries, ligaments, joint instability, menstrual cycle, ovulation, hormones, and contraceptives. Investigators independently dually abstracted and reviewed study details and quality using predefined criteria and evaluated overall strength of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria.

Results: Twenty-one studies totaling 68,758 participants were included: 5 on the menstrual cycle and ACL injury, 7 on hormonal contraceptives and ACL injury, as well as 13 on menstrual cycle and ligament laxity. Four of 5 studies of women not using hormonal contraception indicated that the luteal phase was the least associated with ACL injuries. The 2 largest and highest quality studies on hormonal contraceptives suggested that hormonal contraceptives may be protective against ACL injury. Six of 12 studies on ACL laxity provided quantitative data for meta-analysis, finding significantly increased laxity during the ovulatory phase compared with the follicular phase.

Conclusion: The literature suggests an association between hormonal fluctuations and ACL injury. Recent studies have suggested that oral contraceptives may offer up to a 20% reduction in risk of injury. The literature on ACL injuries and the menstrual cycle has more than doubled over the past decade, permitting quantitative analysis for the first time. However, the overall strength of this evidence is low. Promising potential directions for future research include long-term observational studies with ongoing hormonal assays and large interventional trials of follicular suppression, including newer hormonal methods.

Keywords: anterior cruciate ligament; female; hormonal contraceptives; human; knee injury; menstrual cycle; meta-analysis; sports medicine; systematic review.

Conflict of interest statement

The authors declared that they have no conflicts of interest in the authorship and publication of this contribution.

Figures

Figure 1.
Figure 1.
Literature flowchart. Background refers to articles that did not provide data but were helpful as background reading for the topic. *Studies overlap.
Figure 2.
Figure 2.
Fluctuations in estradiol and progesterone Levels. *Adapted from Speroff and Fritz.
Figure 3.
Figure 3.
Meta-analysis: knee laxity in follicular versus ovulatory phases.

References

    1. Adachi N, Nawata K, Maeta M, Kurozawa Y. Relationship of the menstrual cycle phase to anterior cruciate ligament injuries in teenaged female athletes. Arch Orthop Trauma Surg. 2008;128:473–478.
    1. Agel J, Bershadsky B, Arendt EA. Hormonal therapy: ACL and ankle injury. Med Sci Sports Exerc. 2006;38:7–12.
    1. Arendt EA, Bershadsky B, Agel J. Periodicity of noncontact anterior cruciate ligament injuries during the menstrual cycle. J Gend Specif Med. 2002;5(2):19–26.
    1. Beck NA, Lawrence JT, Nordin JD, DeFor TA, Tompkins M. ACL tears in school-aged children and adolescents over 20. Pediatrics. 2017;139(3):E20161877.
    1. Belanger MJ, Moore DC, Crisco JJ, 3rd, Fadale PD, Hulstyn MJ, Ehrlich MG. Knee laxity does not vary with the menstrual cycle, before or after exercise. Am J Sports Med. 2004;32:1150–1157.
    1. Beynnon BD, Bernstein IM, Belisle A, et al. The effect of estradiol and progesterone on knee and ankle joint laxity. Am J Sports Med. 2005;33:1298–1304.
    1. Beynnon BD, Johnson RJ, Braun S, et al. The relationship between menstrual cycle phase and anterior cruciate ligament injury: a case-control study of recreational alpine skiers. Am J Sports Med. 2006;34:757–764.
    1. Bjordal JM, Arnøy F, Hannestad B, Strand T. Epidemiology of anterior cruciate ligament injuries in soccer. Am J Sports Med. 1997;25:341–345.
    1. Carcia CR, Shultz SJ, Granata KP, Gansneder BM, Perrin DH. Knee ligament behavior following a controlled loading protocol does not differ by menstrual cycle day. Clin Biomech (Bristol, Avon). 2004;19:1048–1054.
    1. Chandrashekar N, Slauterbeck J, Hashemi J. Sex-based differences in the anthropometric characteristics of the anterior cruciate ligament and its relation to intercondylar notch geometry: a cadaveric study. Am J Sports Med. 2005;33:1492–1498.
    1. Chappell JD, Yu B, Kirkendall DT, Garrett WE. A comparison of knee kinetics between male and female recreational athletes in stop-jump tasks. Am J Sports Med. 2002;30:261–267.
    1. Cheung EC, Boguszewski DV, Joshi NB, Wang D, McAllister DR. Anatomic factors that may predispose female athletes to anterior cruciate ligament injury. Curr Sports Med Rep. 2015;14:368–372.
    1. Daniel DM, Stone ML, Sachs R, Malcom L. Instrumented measurement of anterior knee laxity in patients with acute anterior cruciate ligament disruption. Am J Sports Med. 1985;13:401–407.
    1. Deie M, Sakamaki Y, Sumen Y, Urabe Y, Ikuta Y. Anterior knee laxity in young women varies with their menstrual cycle. Int Orthop. 2002;26:154–156.
    1. Dragoo JL, Castillo TN, Braun HJ, Ridley BA, Kennedy AC, Golish SR. Prospective correlation between serum relaxin concentration and anterior cruciate ligament tears among elite collegiate female athletes. Am J Sports Med. 2011;39:2175–2180.
    1. Dragoo JL, Lee RS, Benhaim P, Finerman GAM, Hame SL. Relaxin receptors in the human female anterior cruciate ligament. Am J Sports Med. 2003;31:577–584.
    1. Everhart JS, Flanigan DC, Chaudhari AM. Anteromedial ridging of the femoral intercondylar notch: an anatomic study of 170 archival skeletal specimens. Knee Surg Sports Traumatol Arthrosc. 2014;22:80–87.
    1. Faryniarz DA, Bhargava M, Lajam C, Attia ET, Hannafin JA. Quantitation of estrogen receptors and relaxin binding in human anterior cruciate ligament fibroblasts. In Vitro Cell Dev Biol Anim. 2006;42:176–181.
    1. Ford KR, Myer GD, Hewett TE. Valgus knee motion during landing in high school female and male basketball players. Med Sci Sports Exerc. 2003;35:1745–1750.
    1. Gray AM, Gugala Z, Baillargeon JG. Effects of oral contraceptive use on anterior cruciate ligament injury epidemiology. Med Sci Sports Exerc. 2015;48:648–654.
    1. Harris R, Atkins D, Berg A, Best D, Eden K, Feightner J. US Preventive Services Task Force Procedure Manual. Rockville, MD: Agency for Healthcare Research and Quality; 2001.
    1. Hashemi J, Chandrashekar N, Gill B, et al. The geometry of the tibial plateau and its influence on the biomechanics of the tibiofemoral joint. J Bone Joint Surg Am. 2008;90:2724–2734.
    1. Hashemi J, Mansouri H, Chandrashekar N, Slauterbeck JR, Hardy DM, Beynnon BD. Age, sex, body anthropometry, and ACL size predict the structural properties of the human anterior cruciate ligament. J Orthop Res. 2011;29:993–1001.
    1. Hertel J, Williams NI, Olmsted-Kramer LC, Leidy HJ, Putukian M. Neuromuscular performance and knee laxity do not change across the menstrual cycle in female athletes. Knee Surg Sports Traumatol Arthrosc. 2006;14:817–822.
    1. Hewett TE, Zazulak BT, Myer GD. Effects of the menstrual cycle on anterior cruciate ligament injury risk: a systematic review. Am J Sports Med. 2007;35:659–668.
    1. Hicks-Little C, Thatcher J, Hauth J, Goldfuss A, Cordova M. Menstrual cycle stage and oral contraceptive effects on anterior tibial displacement in collegiate female athletes. J Sports Med Phys Fitness. 2007;47:255–260.
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–560.
    1. Hoffman M, Harter RA, Hayes BT, Wojtys EM, Murtaugh P. The interrelationships among sex hormone concentrations, motoneuron excitability, and anterior tibial displacement in women and men. J Athl Train. 2008;43:364–372.
    1. Hudek R, Fuchs B, Regenfelder F, Koch P. Is noncontact ACL injury associated with the posterior tibial and meniscal slope? Clin Orthop Relat Res. 2011;469:2377–2384.
    1. Khowailed IA, Petrofsky J, Lohman E, Daher N, Mohamed O. 17β-Estradiol induced effects on anterior cruciate ligament laxness and neuromuscular activation patterns in female runners. J Womens Health (Larchmt). 2015;24:670–680.
    1. Kontopantelis E, Reeves D. Performance of statistical methods for meta-analysis when true study effects are non-normally distributed: a simulation study. Stat Methods Med Res. 2012;21:409–426.
    1. Lee H, Petrofsky JS, Daher N, Berk L, Laymon M, Khowailed IA. Anterior cruciate ligament elasticity and force for flexion during the menstrual cycle. Med Sci Monit. 2013;19:1080–1088.
    1. Lefevre N, Bohu Y, Klouche S, Lecocq J, Herman S. Anterior cruciate ligament tear during the menstrual cycle in female recreational skiers. Orthop Traumatol Surg Res. 2013;99:571–575.
    1. Lipps DB, Oh YK, Ashton-Miller JA, Wojtys EM. Morphologic characteristics help explain the gender difference in peak anterior cruciate ligament strain during a simulated pivot landing. Am J Sports Med. 2012;40:32–40.
    1. Liu SH, al-Shaikh R, Panossian V, et al. Primary immunolocalization of estrogen and progesterone target cells in the human anterior cruciate ligament. J Orthop Res. 1996;14:526–533.
    1. Malinzak RA, Colby SM, Kirkendall DT, Yu B, Garrett WE. A comparison of knee joint motion patterns between men and women in selected athletic tasks. Clin Biomech (Bristol, Avon). 2001;16:438–445.
    1. Mather RC, 3rd, Koenig L, Kocher MS, et al. Societal and economic impact of anterior cruciate ligament tears. J Bone Joint Surg Am. 2013;95:1751–1759.
    1. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–269.
    1. Morton S, Levit L, Berg A, Eden J. Finding What Works in Health Care: Standards for Systematic Reviews. Washington, DC: Institute of Medicine; 2011.
    1. Park SK, Stefanyshyn DJ, Ramage B, Hart DA, Ronsky JL. Relationship between knee joint laxity and knee joint mechanics during the menstrual cycle. Br J Sports Med. 2009;43:174–179.
    1. Prior JC, Naess M, Langhammer A, Forsmo S. Ovulation prevalence in women with spontaneous normal-length menstrual cycles—a population-based cohort from HUNT3, Norway. PLoS One. 2015;10:E0134473
    1. Rahr-Wagner L, Thillemann TM, Mehnert F, Pedersen AB, Lind M. Is the use of oral contraceptives associated with operatively treated anterior cruciate ligament injury? A case-control study from the Danish Knee Ligament Reconstruction Registry. Am J Sports Med. 2014;42:2897–2905.
    1. Relevo R, Paynter R. Peer Review of Search Strategies. Methods Research Report (Prepared by the Oregon Evidence-based Practice Center under Contract No. 290-2007-100572). AHRQ Publication No. 12-EHC068-EF Rockville, MD: Agency for Healthcare Research and Quality; 2012.
    1. Ruedl G, Ploner P, Linortner I, et al. Are oral contraceptive use and menstrual cycle phase related to anterior cruciate ligament injury risk in female recreational skiers? Knee Surg Sports Traumatol Arthrosc. 2009;17:1065–1069.
    1. Sciore P, Frank CB, Hart DA. Identification of sex hormone receptors in human and rabbit ligaments of the knee by reverse transcription-polymerase chain reaction: evidence that receptors are present in tissue from both male and female subjects. J Orthop Res. 1998;16:604–610.
    1. Shelbourne KD, Davis TJ, Klootwyk TE. The relationship between intercondylar notch width of the femur and the incidence of anterior cruciate ligament tears. A prospective study. Am J Sports Med. 1998;26:402–408.
    1. Shultz SJ, Sander T, Kirk S, Perrin D. Sex differences in knee joint laxity change across the female menstrual cycle. J Sports Med Phys Fitness. 2005;45:594–603.
    1. Shultz SJ, Schmitz RJ, Beynnon BD. Variations in varus/valgus and internal/external rotational knee laxity and stiffness across the menstrual cycle. J Orthop Res. 2010;29:318–325.
    1. Speroff L, Fritz MA. Clinical Gynecologic Endocrinology and Infertility. 7th ed New York, NY: Lippincott Williams & Wilkins; 2005.
    1. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. JAMA. 2000;283:2008–2012.
    1. Sugimoto D, Alentorn-Geli E, Mendiguchía J, Samuelsson K, Karlsson J, Myer GD. Biomechanical and neuromuscular characteristics of male athletes: implications for the development of anterior cruciate ligament injury prevention programs. Sports Med. 2015;45:809–822.
    1. Todd MS, Lalliss S, Garcia ES, DeBerardino TM, Cameron KL. The relationship between posterior tibial slope and anterior cruciate ligament injuries. Am J Sports Med. 2010;38:63–67.
    1. Van Eck CF, Martins CA, Vyas SM, Celentano U, van Dijk CN, Fu FH. Femoral intercondylar notch shape and dimensions in ACL-injured patients. Knee Surg Sports Traumatol Arthrosc. 2010;18:1257–1262.
    1. Wojtys EM, Huston LJ, Boynton MD, Spindler KP, Lindenfeld TN. The effect of the menstrual cycle on anterior cruciate ligament injuries in women as determined by hormone levels. Am J Sports Med. 2002;30:182–188.
    1. Wolters F, Vrooijink SH, Van Eck CF, Fu FH. Does notch size predict ACL insertion site size? Knee Surg Sports Traumatol Arthrosc. 2011;19:17–21.
    1. Yu WD, Liu SH, Hatch JD, Panossian V, Finerman GA. Effect of estrogen on cellular metabolism of the human anterior cruciate ligament. Clin Orthop Relat Res. 1999;366:229–238.
    1. Yu WD, Panossian V, Hatch JD, Liu SH, Finerman GA. Combined effects of estrogen and progesterone on the anterior cruciate ligament. Clin Orthop Relat Res. 2001;383:268–281.
    1. Zeller BL, McCrory JL, Kibler WB, Uhl TL. Differences in kinematics and electromyographic activity between men and women during the single-legged squat. Am J Sports Med. 2003;31:449–456.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner